We propose to examine the morphology and cytoarchitecture of dopamine (DA)-containing nuerons of the stubstantia nigra and substance P or GABA-containing nuerons of the striatium and the morphological and synaptic relationship between striatonigral SP or GABA and nigrostriatal DA pathways in the aged brain. An integrated methodological approach encompassing light and electron immunocytochemistry, electron microscopy, fluorescence histochemistry, Golgi staining and computer assisted tracing techniques will be used to define the histopathology of the SN and striatum in young and old mouse brain and the distribution of fiber projections and receptive dendritic fields of DA neurons of the SN and "medium spiny neurons' of the striatum. Simultaneous monoamine histofluorescence-neuropeptide immunocytochemistry will be employed to delineate the morphological relationship between striatonigral SP or GABA and nigrostriatal DA pathways in young and old brain. Data will be correlated between advancing age and morphological indices of neurotransmitter pathways of the SN and striatum in order to refine our appreciation of the biological alterations which appear to be central in pathogenesis of movement disorders associated with aging. In addition, information concerning neuronal plasticity of nigral DA or striatel peptide neurons associated with advancing age will provide an added understanding of the potential for neuronal response to possible degeneration of neighboring and/or projecting neurons in the old brain.